The use of a novel tobacco-substitute sheet and smoke dilution to reduce toxicant yields in cigarette smoke

► We describe the use of a glycerol bearing tobacco-substitute sheet in cigarettes. ► In cigarettes it dilutes mainstream smoke with glycerol and reduces machine measured yields of a number of smoke toxicants. ► Responses of in-vitro assays to mainstream smoke condensate are reduced in line with the extent of dilution. ► Exposure of smokers to nicotine, smoke particulates and NNK were reduced in human trials with these cigarettes. ► The sensory character of the smoke, and reduction of some toxicants remain technical challenges. The Institute of Medicine encouraged the pursuit and development of potential reduced-exposure products, tobacco products that substantially reduce exposure to one or more tobacco toxicants and can reasonably be expected to reduce the risk of one or more specific diseases or other adverse health effects. One approach to reducing smoke toxicant yields is to dilute the smoke with glycerol. We report chemical, biological and human exposure data related to experimental cigarettes containing up to 60% of a novel glycerol containing “tobacco-substitute” sheet. Analysis of mainstream smoke from experimental cigarettes showed reductions in yields of most measured constituents, other than some volatile species. In vitro toxicological tests showed reductions in the activity of smoke particulates in proportion to their glycerol content. Human exposure to nicotine was reduced by a mean of 18% as determined by filter studies and by 14% using 24h urinary biomarker analysis. Smoke particulate exposures were reduced by a mean of 29% in filter studies and NNK exposure by similar amounts based on urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol concentrations. These results show that reducing exposure to some smoke toxicants is possible using a tobacco-substitute sheet, although some smoke toxicants, and the sensory attributes of the smoke, remain as technical challenges.